Suramab, a novel antiangiogenic agent, reduces tumor growth and corneal neovascularization

Purpose

Oncological and ophthalmological diseases are increasingly treated with antiangiogenic agents. These agents have different intensities and duration of effects that should be considered to choose the most suitable therapy. Our purpose was to evaluate the synergistic effect of two drugs, jointly administered as a pharmaceutical compound, in two animal models.

Methods

Corneal neovascularization was induced in three groups of nine white New Zealand rabbits, applying a filter paper disk soaked in 1 M NaOH on the central cornea (Ormerod et al., Invest Ophthalmol Vis Sci 30:2148–2153, 1989). Group one was treated immediately after injury with intravenous Suramab, compound of Bevacizumab + Suramin, and group two with intravenous Bevacizumab. A third group of non-treated rabbits was included as control group. Digital photographs were taken at days 9, 15, 21, and 35. Neovessel index (NVI) was calculated using the Image J Program. Neovessels formation was quantified and given a score from 0 to 4 to each quadrant according to the centripetal growth of the longest vessel. Colorectal animal model: 6- to 8-week-old male BALB/c mice were inoculated with cancer cells. Seven days after tumor inoculation, four groups of BALB/c mice were treated with intravenous Bevacizumab (n = 9); intravenous Suramin (n = 10); intravenous Suramab (n = 10); and intravenous saline solution (n = 4). Tumor growth was assessed twice weekly by caliper measurement.

Results

The NVI was remarkably inferior in the group of rabbits treated with intravenous Suramab compared with controls after 35 days of follow-up. A greater inhibitory effect was obtained with Suramab compared to that obtained with Bevacizumab. Suramab significantly reduced tumor volume and prolonged survival of mice compared to controls.

Conclusions

Suramab strongly reduced neovascularization in a rabbit model of corneal angiogenesis and induced a potent antitumoral effect in mice.     

Injury depth control from combined wavelength and power tuning in scanned beam laser thermal therapy

Laser thermal therapy represents a possible method to treat premalignant epithelial lesions of the esophagus. Dynamically conforming the thermal injury profile to a specific lesion boundary is expected to improve the efficacy of such a treatment and avoid complications. In this work, we investigated wavelength tuning as a mechanism to achieve this aimed control over injury depth by using the strong variation of water absorption close to 1900 nm. We developed a numerical model simulating in steps the photon propagation in the tissue, the diffusion of the absorbed heat, and the resulting tissue damage. The model was compared with experimental results on porcine esophageal specimens ex vivo and showed good agreement. Combined with power tuning, the wavelength agility in the range of 1860 to 1895 nm extends the injury range compared to a fixed wavelength source beyond 1 mm, while at the same time improving control over shallow depths and avoiding vaporization at the tissue surface. The combination of two or three discrete wavelengths combined at variable ratios provides similar control, and may provide an improved strategy for the treatment of endothelial lesions.     

Thermal denaturation assays in chemical biology

Thermal denaturation-based methods are becoming increasingly used to characterize protein stability and interactions. Recent technical advances have made these methods more suitable for high throughput screening. Reasonable throughput and the ability to perform these screens using commonly used instruments, such as RT-PCR machines or simple plate readers equipped with heating devices, facilitate these experiments in almost any laboratory. Introducing an aggregation-based monitoring approach as well as alternative fluorophores has allowed the screening of a wider range of proteins, including membrane proteins, against large chemical libraries. Thermal denaturation-based methods are independent of protein function, which is especially useful for the identification of orphan protein function. Here, we review applications of thermal denaturation-based methods in characterizing protein stability and ligand binding, and also provide information on protocol modifications that may further increase throughput.     

Early tissue response to citric acid-based micro- and nanocomposites

A polymerizable superoxide dismutase mimetic (SODm) was incorporated into poly(ethylene glycol) (PEG) hydrogels to protect encapsulated cells from superoxide-mediated damage. Superoxide and other small reactive oxygen species (ROS) can cause oxidative damage to donor tissue encapsulated within size exclusion barrier materials. To enzymatically breakdown ROS within biomaterial cell encapsulation systems, Mn(III) Tetrakis[1-(3-acryloxy-propyl)-4-pyridyl] porphyrin (MnTTPyP-acryl), a polymerizable manganese metalloporphyrin SOD mimetic, was photopolymerized with PEG diacrylate (PEGDA) to create functional gels. In unmodified PEG hydrogels, a significant reduction in metabolic activity was observed when encapsulated Min6 β-cells were challenged with chemically generated superoxide. Cells encapsulated within MnTPPyP-co-PEG hydrogels, however, demonstrated greatly improved metabolic activity following various superoxide challenges. Further, cells were encapsulated and cultured for 10 days within MnTPPyP-co-PEG hydrogels and challenged with superoxide on days 4, 6, and 8. At the conclusion of this study, cells in blank PEG hydrogels had no observable metabolic activity but when encapsulated in MnTPPyP-functionalized hydrogels, cells retained 60 ± 5% of the metabolic activity compared to untreated controls.     

Management of type 2 diabetes: evolving strategies for the treatment of patients with type 2 diabetes

The prevalence of type 2 diabetes continues to increase at an alarming rate around the world, with even more people being affected by prediabetes. Although the pathogenesis and long-term complications of type 2 diabetes are fairly well known, its treatment has remained challenging, with only half of the patients achieving the recommended hemoglobin A_1c target. This narrative review explores the pathogenetic rationale for the treatment of type 2 diabetes, with the view of fostering better understanding of the evolving treatment modalities. The diagnostic criteria including the role of hemoglobin A_1c in the diagnosis of diabetes are discussed. Due attention is given to the different therapeutic maneuvers and their utility in the management of the diabetic patient. The evidence supporting the role of exercise, medical nutrition therapy, glucose monitoring, and antiobesity measures including pharmacotherapy and bariatric surgery is discussed. The controversial subject of optimum glycemic control in hospitalized and ambulatory patients is discussed in detail. An update of the available pharmacologic options for the management of type 2 diabetes is provided with particular emphasis on newer and emerging modalities. Special attention has been given to the initiation of insulin therapy in patients with type 2 diabetes, with explanation of the pathophysiologic basis for insulin therapy in the ambulatory diabetic patient. A review of the evidence supporting the efficacy of the different preventive measures is also provided.